J&J Mesh Approved by FDA Based on Recalled Device

(Corrects description of complications and number of
surgeries cited by patient advocate in the 19th paragraph, and
deletes incorrect quote in the 20th.)

Johnson & Johnson (JNJ), the world’s
second-biggest health-care products maker, is battling lawsuits
over a vaginal implant based on a similar device pulled from the
market more than a decade ago for safety reasons.

The complaints are the latest to implicate the approval
process for medical devices at the U.S. Food and Drug
Administration, which has cleared faulty hip implants and
malfunctioning defibrillators.

In the case of vaginal mesh implants, the FDA continued
approving the hammock-like devices made by J&J and other
companies based on their similarity to Boston Scientific Corp. (BSX)’s
ProteGen even after it was pulled amid safety complaints. Today,
the makers of the entire category of implants face more than 600
lawsuits from women who claim the devices caused serious injury.

“The FDA got caught with their pants down,” said Thomas
Margolis, a pelvic surgeon in Burlingame, California, who treats
patients for mesh complications. “The ProteGen should have told
them, ‘Wait a minute, all of these mesh systems are bad.’”

The devices treat incontinence and a condition called
pelvic organ prolapse, in which internal organs slump into the
vagina. They were allowed on the market as result of the
agency’s approval process, known as 510(k), which relies on the
notion that if one device has been cleared by the FDA then
similar devices need little if any testing in patients.

Under Pressure

The FDA is under increasing pressure to change the system.
Following a year of headlines about defective hip prosthetics,
Congress has been pushing the agency for an overhaul of 510(k).

In July, the FDA issued a statement saying it is unclear
whether prolapse implants provide any benefit over traditional
surgery. The statement came three years after the agency first
acknowledged a problem in a 2008 report that said mesh
complications were serious, if rare. An advisory panel of
physicians said last month that the FDA should demand more
clinical testing of the devices.

“We learn from experience,” Jeffrey Shuren, the director
of the FDA’s Center for Devices and Radiological Health said in
an interview. “What you’re seeing now is the agency taking very
targeted actions against specific devices where we have new
information to suggest we should be taking a different
approach.”

Safe Products

J&J says its vaginal mesh products are safe. Its Gynecare
TVT, which was based on the Boston Scientific product, remains
the “standard of care” for incontinence, said Matthew Johnson,
a spokesman for the New Brunswick, New Jersey-based company. The
device’s safety and efficacy have been demonstrated “by more
than thirteen years of clinical data,” he said in an e-mail.

The chain of approvals that began with Boston Scientific’s
device highlight a key flaw in the 510(k) process, said Amy
Allina, a policy director at the National Women’s Health
Network, a Washington-based advocacy group.

The system lets manufacturers win clearance for a product
by citing its similarity to an already approved device, known in
FDA jargon as a “predicate.” That second device can be cited
as the basis for a third, the third to clear a fourth and so on.

“If a first iteration is recalled, they don’t necessarily
look at the second, third or fourth things that are based on
that,” Allina said in an interview. The system, she said, “is
a mess.”

‘Substantially Equivalent’

The story began in 1996, when Boston Scientific won
clearance for ProteGen, the first vaginally implanted mesh
designed specifically to treat incontinence. Two years later,
J&J won approval for a similar device, called Gynecare TVT.
Under the 510(k) system, J&J wasn’t required to conduct human
testing because the company claimed its device was
“substantially equivalent” to the Boston Scientific device.

A year later, Boston Scientific voluntarily pulled about
20,000 ProteGen meshes, saying it had received 123 reports of
problems, including discomfort, painful sex, and erosion of
vaginal tissue. Nonetheless, J&J and at least two other
manufacturers, American Medical Systems and Covidien Plc (COV), soon
came out with products that traced their design back to
ProteGen.

The FDA has said it doesn’t know the number of women who
have received the implants since 1998, though it estimates
almost 300,000 were used in 2010.

510(k) System

All were approved through the 35-year-old 510(k) system,
used by the FDA to review some 90 percent of device applications
each year. The same process was used to clear the 93,000
artificial hips pulled by J&J last year due to high failure
rates, as well as hundreds of external heart defibrillators
recalled since 2005 by Minneapolis-based Medtronic Inc. (MDT)

Designed to vet low-risk devices such as surgical drapes,
510(k) also become a gateway for items like joint implants and
vaginal mesh that can claim a tie to older products, said Diana Zuckerman, president of the National Research Center for Women &
Families, a Washington advocacy group that has pushed for more
device testing.

Patients who received the devices say the result has been
years of pain. Lana Keeton, a 64-year-old steel broker and
patient advocate from Austin, Texas, said she received her J&J
implant in December 2001 to treat incontinence symptoms
following a hysterectomy.

Once implanted, the rough edges of the synthetic fabric
began cutting into her bladder, she said in an interview. Keeton
said she has undergone 17 medical procedures, including six
surgeries, to trim off those edges. Because the mesh has become
embedded in her tissue, doctors still haven’t gotten all of it
out, she said.

‘Removing Gum’

“It’s like removing gum from your hair,” she said.

Keeton’s lawsuit was dismissed by a federal judge in Miami
in August 2007. U.S. District Judge Ursula Ungaro threw out the
case before it reached a trial, ruling Keeton “has not produced
sufficient evidence” to support her claim, according to court
documents. Undeterred, she went on to found Truth in Medicine, a
nonprofit group pushing for a recall of the devices. She also
works as a paid consultant and researcher for attorneys suing
mesh manufacturers.

J&J still faces more than 270 suits from women like Marian
Goldberg, a retired social worker from New York. Goldberg, 66,
received the TVT and another vaginal mesh, J&J’s Prolift, in
2007. Since then, she said, the devices’ failure has led to
permanent pain, nerve damage and incontinence worse than the
original condition the meshes were meant to treat.

The TVT was “approved without being tested on its own
merits. That in itself is unconscionable,” Goldberg said in a
telephone interview. “Then to have been allowed to stay on the
market when it was modeled on a device that was already impaired
is unbelievable.”

FDA Concern

In a report released in January, the FDA acknowledged
concern about the use of recalled predicates, saying the
practice could “put patients at risk.” The agency said it
would consider 25 changes to the 510(k) system this year,
including stricter guidelines on what products can be cited to
back new devices.

In July, the U.S. Institute of Medicine, a non-profit that
advises the government on medical issues, warned of risks from
clearing devices based on old products. About 29 percent of
devices cleared through 510(k) are no longer on the market, and
though the FDA often can’t say why they were pulled, they remain
available to cite as proof of new products’ safety, the report
said.

Boston Scientific cited five predicates for ProteGen,
including hernia slings and fabric used in cardiac surgery, FDA
records show. Two years later, J&J named ProteGen as a basis for
the Gynecare TVT, noting in its application that
“technologically, both the new device and predicate device are
the same.”

Voluntary Recall

By that time, complaints about Boston Scientific’s device
were already filtering into the FDA. A year after J&J’s TVT won
clearance, Boston Scientific voluntarily recalled about 20,000
of its meshes.

J&J’s Gynecare TVT later became a predicate for the IVS
Tunneller I, made by Dublin-based Covidien, and the Sparc Sling,
made by the American Medical Systems unit of Endo
Pharmaceuticals Holdings Inc. (ENDP), based in Chadds Ford,
Pennsylvania. Those, in turn, were cited to clear future
versions, each said to be “substantially equivalent” to its
predecessors, according to FDA records.

It’s unclear what steps, if any, the FDA took at the time
of the Boston Scientific recall to scrutinize other meshes. The
agency didn’t respond to requests for information about how it
handled the ProteGen and similar products. In 2003, Boston
Scientific settled 738 suits over its mesh for an undisclosed
sum.

Safety Debate

The safety debate has presented a conundrum for
manufacturers, who have avoided clinical tests for the devices
by calling them similar to one another yet now say the products
have advanced far beyond the earlier versions.

“There are much more modern and improved devices out
there,” said Ginger Glaser, a senior regulatory affairs
director for American Medical Systems. “It’s not necessarily,
‘if this one was a problem, all the other ones are a problem,’”
she said.

The FDA advisory panel disagreed. The 17-member group,
comprised mostly of pelvic surgeons, recommended at last month’s
hearing that some vaginal meshes be reclassified as high-risk
devices requiring new studies to stay on the market.

While the devices may still prove a viable option for well-
trained surgeons, there’s not enough evidence to say that all
are “ready for prime time,” panelist Cheryl Iglesia, a surgeon
and associate professor at Georgetown University Medical Center,
said during the hearing.

The FDA appears to be inching toward a similar decision. At
the September hearing, Colin Pollard, director of the FDA’s
obstetrics and gynecology devices branch, said it may take as
long as three years to issue new rules. Until then, current
models can stay on the market, he said.

That’s too late for many women, said Allina, of the
National Women’s Health Network.

“There are women who have these products inside of them
and are living with the harm that was done to them,” she said.
“It’s a terrifying thing to roll the dice with.”